Interrelations Between Bacterial Infection, Inflammation, and Thrombosis on Biomedical Devices

生物医疗器械上细菌感染、炎症和血栓形成之间的相互关系

• 批准号: 9632568
• 负责人: Eric Kaler
• 金额: $ 26.03万
• 依托单位: University of Delaware
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-09-01 至 2000-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9632568&HistoricalAwards=false
• 关键词: Interrelations; Between; Bacterial; Infection; Inflammation

9632568 Cooper Clinical infections are one of the greatest problems associated with synthetic implanted devices. Such infections account for more than 45% of hospital infections, associated with indwelling catheters and surgery for joint replacement, and bypass operations. Such infections are also more difficult to treat than conventional infections. With over 200 million intravascular devices sold annually, it is clear that infections associated with biomedical devices pose a huge problem in clinical medicine. Understanding the mechanisms by which the bacteria responsible for such infections adhere to implants and resist antibiotic treatment is an important step in developine materials that resist bacterial growth, and improving therapy for implant-associated infections. The use of plastic materials for implants is not only associated with risk of infection, but also risk of clot formation (thrombosis), and inflammation around the site. Little is known about the specific mechanisms that govern the complex relationships between infections, inflammation, and thrombosis. Factors that may affect this relationship are the surface chemistry of the device, the proteins that may be absorbed from the blood after implantation, and the surface chemistry of the bacteria and blood cells. The focus of this research will be to investigate the cellular adhesion and activation events that infection, inflammation, and thrombosis have in common, and to determine their individual effects on the other processes. Specifically, the influence that protein and cellular components of thrombi (e.g. fibrin and blood platelets) have in mediating bacterial adhesion and colonization on artificial surfaces will be investigated. The effects of adherent bacteria on platelet adhesion and activation will also be studied. Another important factor that will be investigated is the change in the metabolic state of adherent bacteria on thrombi and on implant surfaces. The adhesion, activa tion, and accompanying shape changes of white blood cells in the presence of adherent bacteria on chemically modified polyurethanes will be studied. These studies will primarily be carried out using an automated viedomicroscopy system that allows the direct observation of individual cells interacting with different surfaces over a period of time. The study of cell-surface interactions will be carried out on both glass and polyurethane surfaces, as well as model surfaces of self-assembling monolayers. The information obtained in this work will provide a better understanding of the interrelationship between implanted devices, bacterial infection, inflammation, and thrombosis, an how each process may influence the other. Detailed understanding of the mechanisms that govern these relationships will lead to the development of biomaterials that resist microbial adhesion and proliferation as well as thrombosis. Ultimately, studies such as these are important in improving patient welfare and reducing health care costs. ***

9632568 Cooper 临床感染是与合成植入装置相关的最大问题之一。 此类感染占医院感染的 45% 以上，与留置导管、关节置换手术和搭桥手术相关。 此类感染也比传统感染更难治疗。 每年销售超过 2 亿个血管内装置，显然与生物医学装置相关的感染在临床医学中构成了巨大的问题。 了解引起此类感染的细菌粘附在植入物上并抵抗抗生素治疗的机制是开发抵抗细菌生长的材料和改进植入物相关感染治疗的重要一步。 使用塑料材料制造植入物不仅会带来感染风险，还会带来凝块形成（血栓形成）和部位周围炎症的风险。 人们对控制感染、炎症和血栓形成之间复杂关系的具体机制知之甚少。 可能影响这种关系的因素包括装置的表面化学、植入后可能从血液中吸收的蛋白质以及细菌和血细胞的表面化学。 这项研究的重点将是研究感染、炎症和血栓形成所共有的细胞粘附和激活事件，并确定它们对其他过程的个体影响。 具体来说，将研究血栓的蛋白质和细胞成分（例如纤维蛋白和血小板）对介导人工表面上的细菌粘附和定植的影响。 还将研究粘附细菌对血小板粘附和活化的影响。 将要研究的另一个重要因素是血栓和植入物表面上粘附细菌的代谢状态的变化。 将研究在化学改性聚氨酯上存在粘附细菌的情况下白细胞的粘附、激活和伴随的形状变化。 这些研究将主要使用自动视频显微镜系统进行，该系统可以直接观察一段时间内与不同表面相互作用的单个细胞。 细胞-表面相互作用的研究将在玻璃和聚氨酯表面以及自组装单分子层的模型表面上进行。 这项工作中获得的信息将有助于更好地理解植入设备、细菌感染、炎症和血栓形成之间的相互关系，以及每个过程如何影响另一个过程。 详细了解控制这些关系的机制将有助于开发抵抗微生物粘附和增殖以及血栓形成的生物材料。 最终，此类研究对于改善患者福利和降低医疗保健成本非常重要。 ***